Hemophilia A is an X-linked, recessive bleeding disorder caused by deficiency of clotting Factor VIII (“FVII”). In the United States alone there are approximately 20,000 patients with hemophilia A. The clinical presentation for hemophilia A is characterized by episodes of spontaneous and prolonged bleeding. Currently, hemophilia A is treated with protein replacement therapy using either plasma-derived or recombinant FVIII. Although FVIII replacement markedly improved the life expectancy of patients suffering from hemophilia, they are still at risk for severe bleeding episodes and chronic joint damage, since prophylactic treatment is restricted by the short half-life, the limited availability and the high cost of purified FVIII, which can approach $100,000/patient/year. In addition, the use of plasma-derived factors obtained from contaminated blood sources increases the risk of viral transmission. Gene therapy offers the promise of a new method of treating hemophilia A, since the therapeutic window is relatively broad and levels slightly above 1% of normal physiological levels are therapeutic (see, Kay M A, High K. Gene therapy for the hemophilias [comment]. Proc Natl Acad Sci USA. 1999; 96:9973-9975). If successful, gene therapy could provide constant FVIII synthesis which may lead to a cure for this disease. Different viral and non-viral gene therapy methods have been evaluated for the treatment of patients suffering from hemophilia A (see, e.g., Chuah M K, Collen D, VandenDriessche T. Gene therapy for hemophilia: hopes and hurdles. Crit Rev Oncol Hematol. 1998; 28:153-171 and Chuah M K, Collen D, VandenDriessche T. Gene therapy for hemophilia. J Gene Med. 2001; 3:3-20). Adenoviral (Ad) vectors are the most efficient vectors for hepatic gene delivery (Ibid.). The adenoviral vector genome remains episomal, implying that the risk of neoplastic transformation due to insertional mutagenesis is low. However, early-generation adenoviral vectors still contain most viral genes. Their expression contributes to inflammatory responses, toxicity and short-term transgene expression (see, e.g. Yang Y, Su Q, Wilson J M. Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs. J Virol. 1996, 70:7209-7212; Fang B, Wang H, Gordon G, Bellinger D A, Read M S, Brinkhous K M, Woo S L, Eisensmith R C. Lack of persistence of E1-recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs. Gene Ther. 1996, 3:217-222; Schiedner G, Morral N, Parks R J, Wu Y, Koopmans S C, Langston C, Graham F L, Beaudet A L, Kochanek S. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity [published erratum appears in Nat Genet 1998 March; 18(3):298]. Nat Genet. 1998, 18:180-183; Yang Y, Ertl H C, Wilson J M. MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. Immunity. 1994, 1:433-442; Yang Y, Li Q, Ertl H C, Wilson J M. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol. 1995, 69:2004-2015; and Yang Y, Jooss K U, Su Q, Ertl H C, Wilson J M. Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. Gene Ther. 1996; 3:137-144). Studies in the art have shown that injection of early-generation adenoviral vectors encoding canine or human FVIII resulted in efficient liver transduction and in therapeutic levels of FVIII in hemophilic mice, dogs or rhesus macaques (see, e.g., Connelly S, Smith T A, Dhir G, Gardner J M, Mehaffey M G, Zaret K S, McClelland A, Kaleko M. In vivo gene delivery and expression of physiological levels of functional human factor VIII in mice. Hum Gene Ther. 1995, 6:185-193; Connelly S, Gardner J M, McClelland A, Kaleko M. High-level tissue-specific expression of functional human factor VIII in mice. Hum Gene Ther. 1996, 7:183-195; Connelly S, Mount J, Mauser A, Gardner J M, Kaleko M, McClelland A, Lothrop C D, Jr. Complete short-term correction of canine hemophilia A by in vivo gene therapy. Blood. 1996, 88:3846-3853; Connelly S, Andrews J L, Gallo A M, Kayda D B, Qian J, Hoyer L, Kadan M J, Gorziglia M I, Trapnell B C, McClelland A, Kaleko M. Sustained phenotypic correction of murine hemophilia A by in vivo gene therapy. Blood. 1998, 91:3273-3281; and Gallo-Penn A M, Shirley P S, Andrews J L, Tinlin S, Webster S, Cameron C, Hough C, Notley C, Lillicrap D, Kaleko M, Connelly S. Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs. Blood. 2001; 97:107-113). However, FVIII levels declined to baseline, possibly due to vector toxicity related to residual adenoviral gene expression. In the dog model, induction of antibody immune responses against FVIII was associated with only transient correction of the bleeding diathesis (see, Gallo-Penn, et al. supra). Inflammatory responses and vector toxicity further diminished the therapeutic efficacy (Ibid.). To overcome the limitations of early-generation adenoviral vectors, novel adenoviral vectors have been developed, designated as high-capacity (HC), helper-dependent (HD) or “gutless” adenoviral vectors, which are devoid of all adenoviral genes. These HC-Ad vectors retain only the necessary cis-acting elements that are required for generating infectious vector particles during vector production and typically depends on the use of an E1-complementation cell line and a packaging-defective helper virus that provides the necessary viral functions in trans (see, Kochanek S. High-capacity adenoviral vectors for gene transfer and somatic gene therapy. Hum Gene Ther. 1999, 10:2451-2459 and Parks R J, Chen L, Anton M, Sankar U, Rudnicki M A, Graham F L. A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc Natl Acad Sci USA. 1996, 93:13565-13570). However, notwithstanding the improvements of these HC-Ad vectors, the therapeutic application of said vectors still causes toxicity to the host. This toxicity is mainly due to the need for the use of a high amount of infectious units of recombinant vector and results in the activation of the innate immune system, in liver toxicity and may contribute to the induction of a humoral immune response. Thus, there is a need to apply lower vector doses to reduce undesirable side effects.